While the aetiology of essential hypertension, a disease prevalent in cultured societies, is unknown, there is much evidence to suggest that abnormal sodium metabolism plays a critical role. That is, hypertension can be induced or exaggerated by a large sodium intake and frequently can be treated by limiting sodium intake and/or by administering natriuretics. Hypertension can also be induced by (Na.sup.+ retaining) mineralcorticoids in experimental animals and in man, as a consequence of primary aldosteronism or Cushing's syndrome.
Despite the widely recognized correlation between sodium metabolism and hypertension, the underlying mechansim has escaped elucidation. However, a number of recent observations appear to provide some important clues as to these mechanisms, i.e., (1) that calcium ions are the immediate trigger for contraction in vascular smooth muscle, as in other types of muscle (see Filo, R. S.; Bohr, D. F.; and Ruegg, J. C. Science, 147: 1581-1583 (1972), and (2) that sodium ions play a critical role in the maintenance of calcium balance in vascular smooth muscle. (See Blaustein, M. P., Amer. J. Physiol., 232: C165-C173 (1977).)
It has been postulated that in some "volume-expanded" animal models of hypertension there may be elevated plasma levels of a Na.sup.+ pump inhibitor, i.e, a natriuretic hormone (see Haddy, F. J. et al, Life Sci. 19: 935-948 (1976).) This has led to the hypothesis that an increase in the concentration of an inhibitor of (Na.sup.+ +K.sup.+)ATPase is responsible for the increased peripheral vascular resistance in essential hypertension. That is, this inhibitor promotes both sodium and calcium gain by vascular smooth muscle, causing the increased peripheral vascular resistance which is the hallmark of hypertension. (See Folkow, B. and Neil, E., Circulation, Oxford University Press, pp. 560-583 (1971), and Blaustein, M. P. Amer. J. Physiol., 232: C165-C173 (1977).)
Although various bioassays and cytochemical assays, as disclosed below, have been developed to detect the postulated Na.sup.+ pump inhibitor in essential hypertension, no direct biochemical determination of such a circulating inhibitor has been demonstrated.